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Cardiovascular atherosclerotic and ischemic diseases constitute the leading cause of morbidity and mortality throughout middle- and high-income countries. More efficient preventive and regenerative therapeutic strategies are therefore urgently needed. The repeated finding that putative “endothelial progenitor cells” (EPCs) can efficiently promote angiogenesis and restore perfusion of ischemic tissues has provoked a wealth of studies evaluating and developing their therapeutic potential. In the present review, we discuss the growing knowledge about various distinct cell populations which have been collectively termed “EPCs”, including myeloid cells and progenitor cells of different origin. We also present clinical studies aiming to examine their therapeutic potential for cardiovascular disease. In addition, we will discuss recent insights into mechanisms leading to dysfunction of “EPCs” in cardiovascular disease. Those findings may help to optimize autologous cell-based treatment approaches, as well as to establish cellular dysfunction itself as an interesting novel therapeutic target.